Influence of Organic Solvents on Secondary Brain Damage after Experimental Traumatic Brain Injury.

Johannes Walter,Nikolaus Plesnila,Nicole A Terpolilli,Julian Schwarting

doi:10.1089/neur.2020.0029

Johannes Walter, Nikolaus Plesnila + Show 2 more

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https://doi.org/10.1089/neur.2020.0029

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Abstract

Many compounds tested for a possible neuroprotective effect after traumatic brain injury (TBI) are not readily soluble and therefore organic solvents need to be used as a vehicle. It is, however, unclear whether these organic solvents have intrinsic pharmacological effects on secondary brain damage and may therefore interfere with experimental results. Thus, the aim of the current study was to evaluate the effect of four widely used organic solvents, dimethylsulfoxide (DMSO), Miglyol 812 (Miglyol®), polyethyleneglycol 40 (PEG 40), and N-2-methyl-pyrrolidone (NMP) on outcome after TBI in mice. A total of 143 male C57Bl/6 mice were subjected to controlled cortical impact (CCI). Contusion volume, brain edema formation, and neurological function were assessed 24 h after TBI. Test substances or saline were injected intraperitoneally (i.p.) 10 min before CCI. DMSO, Miglyol, and PEG 40 had no effect on post-traumatic contusion volume after CCI; NMP, however, significantly reduced contusion volume and brain edema formation at different concentrations. The use of DMSO, Miglyol, and PEG 40 is unproblematic for studies investigating neuroprotective treatment strategies as they do not influence post-traumatic brain damage. NMP seems to have an intrinsic neuroprotective effect that should be considered when using this agent in pharmacological experiments; further, a putative therapeutic effect of NMP needs to be elucidated in future studies.

Highlights

Therapy of secondary brain injury is still limited to a few strictly symptomatic treatment options aimed at controlling intracranial pressure (ICP) and cerebral perfusion pressure (CPP), as no interventions directly interacting with the specific pathophysiological pathways of the evolution of secondary brain damage are available.[3,4]
All animals survived to the end of the observation period; no animal was excluded from analysis
Contusion volume 15 min after cortical impact (CCI) was 15.0 – 2.4 mm[3] and significantly expanded to 25.5 – 1.2 mm[3 24] h after trauma induction in the vehicle (PBS) control group; ( p = 0.003, Fig. 2); secondary lesion expansion amounted to 10.5 mm[3] or 41.2% of contusion volume 24 h after CCI

Summary

Introduction

Traumatic brain injury (TBI) is a leading cause of death in children and young adults.[1,2] Despite decades of research, therapy of secondary brain injury is still limited to a few strictly symptomatic treatment options aimed at controlling intracranial pressure (ICP) and cerebral perfusion pressure (CPP), as no interventions directly interacting with the specific pathophysiological pathways of the evolution of secondary brain damage are available.[3,4] Evolution of brain damage following TBI is characterized by two phases: primary damage— occurring at the moment of impact—is not treatable and can only be influenced by preventive measures.

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